PMID- 10395202
OWN - NLM
STAT- MEDLINE
DCOM- 19990719
LR  - 20190826
IS  - 0161-5890 (Print)
IS  - 0161-5890 (Linking)
VI  - 35
IP  - 17
DP  - 1998 Dec
TI  - Role of SHIP in FcgammaRIIb-mediated inhibition of Ras activation in B cells.
PG  - 1135-46
AB  - Previous studies by our lab and others established that co-crosslinking sIg and
      IgG receptor FcgammaRIIb in B cells in a feedback suppression model (negative
      signaling) promoted tyrosine phosphorylation of the inositol 5-phosphatase SHIP
      and its interaction with Shc and that these events were associated with
      inhibition of the Ras pathway. We therefore hypothesized a competition model in
      which the SH2 domain of SHIP competes with that of Grb2 for binding to
      phospho-Shc to inhibit the Ras pathway. Here, we provide evidence consistent with
      this hypothesis. First, FcgammaRIIb-deficient B cells, which do not undergo SHIP 
      tyrosine phosphorylation nor interaction with Shc, displayed an active Ras
      pathway under negative signaling conditions; reconstitution of FcgammaRIIb
      expression restored the block in Ras. Second, under conditions of negative
      signaling leading to SHIP-Shc interaction in wild-type B cells, we observed a
      profound reduction in the activation-induced association of Grb2 to Sos.
      Experiments reported here and elsewhere revealed the Grb2-Sos interaction
      required the engagement of the Grb2 SH2 domain by phospho-Shc. Third, we
      demonstrated that phospho-Shc cannot concomitantly bind Grb2 and SHIP, indicating
      that the two proteins competed for the same phospho-tyrosine residue on Shc.
      These data are consistent with the proposed competition model, and further
      indicate that the activation induced Grb2-Sos association is rate limiting for
      Ras activation.
FAU - Tridandapani, S
AU  - Tridandapani S
AD  - Ohio State University, Department of Microbiology and the Comprehensive Cancer
      Center, Columbus 43210, USA.
FAU - Phee, H
AU  - Phee H
FAU - Shivakumar, L
AU  - Shivakumar L
FAU - Kelley, T W
AU  - Kelley TW
FAU - Coggeshall, K M
AU  - Coggeshall KM
LA  - eng
GR  - AI41447/AI/NIAID NIH HHS/United States
GR  - CA64268/CA/NCI NIH HHS/United States
GR  - P30CA16058/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Mol Immunol
JT  - Molecular immunology
JID - 7905289
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Antigens, CD)
RN  - 0 (Fc gamma receptor IIB)
RN  - 0 (GRB2 Adaptor Protein)
RN  - 0 (Grb2 protein, mouse)
RN  - 0 (Membrane Proteins)
RN  - 0 (Proteins)
RN  - 0 (Receptors, IgG)
RN  - 0 (Son of Sevenless Proteins)
RN  - EC 3.1.3.2 (Phosphoric Monoester Hydrolases)
RN  - EC 3.1.3.86 (INPPL1 protein, human)
RN  - EC 3.1.3.86 (Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases)
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - *Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - Antigens, CD/*metabolism
MH  - B-Lymphocytes/*immunology
MH  - GRB2 Adaptor Protein
MH  - Membrane Proteins/metabolism
MH  - Mice
MH  - Models, Immunological
MH  - Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
MH  - Phosphoric Monoester Hydrolases/*metabolism
MH  - Protein Binding
MH  - Proteins/metabolism
MH  - Receptors, IgG/*metabolism
MH  - Signal Transduction
MH  - Son of Sevenless Proteins
MH  - ras Proteins/*metabolism
MH  - src Homology Domains
EDAT- 1999/07/08 00:00
MHDA- 1999/07/08 00:01
CRDT- 1999/07/08 00:00
PHST- 1999/07/08 00:00 [pubmed]
PHST- 1999/07/08 00:01 [medline]
PHST- 1999/07/08 00:00 [entrez]
AID - S0161589098000972 [pii]
AID - 10.1016/s0161-5890(98)00097-2 [doi]
PST - ppublish
SO  - Mol Immunol. 1998 Dec;35(17):1135-46. doi: 10.1016/s0161-5890(98)00097-2.